Glaucoma is characterized by progressive death of retinal ganglion cells (RGCs) resulting in blindness. The long-term implication of this research is prevention of RGC dysfunction and loss in patients with glaucoma. Our objective is to define the natural history of RGC dysfunction and death in an inbred strain mouse model of glaucoma (DBA/2J) with spontaneously elevated intraocular pressure (lOP). We will use non-invasive and improved methodologies such as Pattern Electroretinogram (PERG), Optical Coherence Tomography (OCT) and non-contact tonometry, as well as an unique non-glaucomatous mouse with DBA genetic background. The central hypothesis is that there is a substantial population of dysfunctional RGCs that can be detected by state-of-the-art structural-functional comparison in a longitudinal evaluation.The rationale is that the characterization of RGC dysfunction and death in a readily available mouse model of glaucoma by means of methods adapted from human clinical examination will provide a powerful experimental system for treating and even reversing the condition in humans. We will focus on two specific aims: 1) To improve methodologies for non-invasive quantification of RGC function/number and lOP, and 2) To monitor the onset and progression of retinopathy in individual animals. The proposed research is innovative, because it is based on non-invasive and sequential monitoring of key variables in glaucoma and unique strains of mice. We are particularly prepared to undertake this study because our research team combines specific expertise in visual electrophysiology, retinal imaging, mouse glaucoma models, and biophysics. Our expectation is that we will be able to determine whether RGC dysfunction precedes RGC death, determine functional and anatomical endpoints for onset and progression, and determine the visual capabilities of surviving RGCs. Such outcomes are significant, since exploiting an animal model for testing neuroprotective strategies that preserve visual function is an important component of future research on treatments for glaucoma.